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Bilateral striatal transplantation of human olfactory stem cells ameliorates motor function, prevents necroptosis-induced cell death and improves striatal volume in the rat model of Huntington’s disease
Journal of Chemical Neuroanatomy ( IF 2.7 ) Pub Date : 2021-03-01 , DOI: 10.1016/j.jchemneu.2020.101903
Amir-Hossein Bayat 1 , Sara Saeidikhoo 2 , Vahid Ebrahimi 3 , Somaye Mesgar 2 , Mohammadjavad Joneidi 2 , Reza Soltani 2 , Fakhroddin Aghajanpour 2 , Ibrahim Mohammadzadeh 2 , Abolfazl Torabi 2 , Mohammad-Amin Abdollahifar 2 , Zohreh Bagher 4 , Rafieh Alizadeh 4 , Abbas Aliaghaei 2
Affiliation  

Cellular transplant therapy is one of the most common therapeutic strategies used to mitigate symptoms of neurodegenerative diseases such as Huntington's disease (HD). Briefly, the main goal of the present study was to investigate HD's motor deficits through the olfactory ecto-mesenchymals stem cells (OE-MSC) secretome. OE-MSCs were characterized immunophenotypically by the positive expression of CD73, CD90 and CD105. Also, three specific markers of OE-MSCs were obtained from the nasal cavity of human volunteers. The main features of OE-MSCs are their high proliferation, ease of harvesting and growth factor secretion. All animals were randomly assigned to three groups: control, 3-NP + vehicle treated and 3-NP + Cell groups. In both experimental groups, the subjects received intraperitoneal 3-NP (30 mg/kg) injections once a day for five consecutive days, followed by the bilateral intra-striatal implantation of OE-MSCs in the 3-NP + Cell group. Muscular function was assessed by electromyography and rotarod test, and the locomotor function was evaluated using the open field test. According to our findings, striatal transplants of OE-MSCs reduced microglial inflammatory factor, the tumor necrosis factor (TNFα) in the 3-NP + Cell group, with a significant reduction in RIP3, the markers of necroptosis in striatum. In addition to the remarkable recovery of the striatal volume after engraftment, the motor activities were enhanced in the 3-NP + cell group compared to the 3-NP + vehicle group. Taken together, our results demonstrated the in vivo advantages of OE-MSCs treatment in an HD rat model with numerous positive paracrine effects including behavioral and anatomical recovery.

中文翻译:

人类嗅觉干细胞的双侧纹状体移植改善运动功能,防止坏死性凋亡诱导的细胞死亡并改善亨廷顿病大鼠模型中的纹状体体积

细胞移植疗法是最常见的治疗策略之一,用于减轻神经退行性疾病(例如亨廷顿病 (HD))的症状。简而言之,本研究的主要目标是通过嗅觉外间充质干细胞 (OE-MSC) 分泌组研究 HD 的运动缺陷。OE-MSCs 的免疫表型特征在于 CD73、CD90 和 CD105 的阳性表达。此外,从人类志愿者的鼻腔中获得了 OE-MSCs 的三个特定标记。OE-MSCs 的主要特征是它们的高增殖、易于收获和生长因子分泌。所有动物被随机分配到三组:对照组、3-NP + 载体治疗组和 3-NP + 细胞组。在两个实验组中,受试者连续五天每天一次腹腔注射 3-NP(30 mg/kg),然后在 3-NP + Cell 组中双侧纹状体内植入 OE-MSC。肌肉功能通过肌电图和旋转棒试验进行评估,运动功能通过旷场试验进行评估。根据我们的研究结果,OE-MSC 的纹状体移植减少了 3-NP + 细胞组中的小胶质细胞炎症因子,即肿瘤坏死因子 (TNFα),显着减少了纹状体坏死性凋亡的标志物 RIP3。除了移植后纹状体体积显着恢复外,与 3-NP + 载体组相比,3-NP + 细胞组的运动活动增强。综合起来,
更新日期:2021-03-01
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